1-(3-(2-Fluoropropan-2-yl)isoxazol-5-yl)-3-(3-hydroxyphenyl)urea → 1-(3-(2-Fluoropropan-2-yl)isoxazol-5-yl)-3-(3-(7-methoxy-6-(3-(methylsulfonyl)propoxy)quinazolin-4-yloxy)phenyl)urea
Reaction equation
[F:1][C:2]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([OH:20])[CH:15]=2)=[O:12])[O:7][N:6]=1)([CH3:4])[CH3:3].Cl[C:22]1[C:31]2[C:26](=[CH:27][C:28]([O:40][CH3:41])=[C:29]([O:32][CH2:33][CH2:34][CH2:35][S:36]([CH3:39])(=[O:38])=[O:37])[CH:30]=2)[N:25]=[CH:24][N:23]=1>>[F:1][C:2]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:22]3[C:31]4[C:26](=[CH:27][C:28]([O:40][CH3:41])=[C:29]([O:32][CH2:33][CH2:34][CH2:35][S:36]([CH3:39])(=[O:37])=[O:38])[CH:30]=4)[N:25]=[CH:24][N:23]=3)[CH:15]=2)=[O:12])[O:7][N:6]=1)([CH3:3])[CH3:4]Participants
Reactant 2
Product 1
Procedure
The title compound was prepared from 1-(3-(2-fluoropropan-2-yl)isoxazol-5-yl)-3-(3-hydroxyphenyl)urea (84 mg, 0.3 mmol) and 4-chloro-7-methoxy-6-(3-(methylsulfonyl)propoxy)quinazoline from Example 41B Step 1 (76 mg, 0.23 mmol) using the procedure described in Example 16C. The crude product was purified by chromatography on silica gel (25-100% EtOAc/hexanes) to afford 1-(3-(2-fluoropropan-2-yl)isoxazol-5-yl)-3-(3-(7-methoxy-6-(3-(methylsulfonyl)propoxy)quinazolin-4-yloxy)phenyl)urea (81 mg, 0.14 mmol, 61%). 1H NMR (300 MHz, DMSO-d6) δ 10.42 (br s, 1H), 9.11 (s, 1H), 8.57 (s, 1H), 7.63-7.58 (m, 2H), 7.47-7.40 (m, 2H), 7.32 (d, 1H), 7.00 (d, 1H), 6.15 (s, 1H), 4.32 (t, 2H), 4.02 (s, 3H), 3.41-3.29 (m, 2H), 3.06 (s, 3H), 2.31-2.22 (m, 2H), 1.66 (d, 6H); LC-MS (ESI) m/z 574 (M+H)+.
Workup
- customThe crude product was purified by chromatography on silica gel (25-100% EtOAc/hexanes)
Sources & evidence
- ORD record
- ord-a229018ed2b64b47bd7fd94d467e80ad
- Source dataset
- uspto-grants-2015_03
- Patent number
- US08969587B2
Reaction notes
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